World Alzheimer Report 2009
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
World Alzheimer Report
2009
Alzheimer’s Disease International World Alzheimer Report 2009 Editors Prof Martin Prince, Institute of Psychiatry, King’s College London (chapter 1–2) Mr Jim Jackson (chapter 3–4) Scientific Group, Institute of Psychiatry, King’s College London Dr Cleusa P Ferri Ms Renata Sousa Dr Emiliano Albanese Mr Wagner S Ribeiro Dr Mina Honyashiki ADI Advocacy Working Group Daisy Acosta (Dominican Republic) Marco Blom (Netherlands) Scott Dudgeon (Canada) Niles Frantz (USA) Angela Geiger (USA) Sabine Jansen (Germany) Andrew Ketteringham (UK) Lindsay Kinnaird (Scotland) Birgitta Martensson (Switzerland) Glenn Rees (Australia) Frank Schaper (Australia) Mike Splaine (USA) Tami Tamitegama (Sri Lanka) Krister Westerlund (Sweden) Marc Wortmann (ADI) ADI would like to thank those who contributed financially: Vradenburg Foundation Geoffrey Beene Foundation – www.geoffreybeene.com/alzheimers.html Alzheimer’s Association – www.alz.org Alzheimer’s Australia – www.alzheimers.org.au Alzheimer’s Australia WA – www.alzheimers.asn.au Alzheimer Scotland – www.alzscot.org Alzheimer’s Society – www.alzheimers.org.uk Association Alzheimer Suisse – www.alz.ch Alzheimerföreningen i Sverige – www.alzheimerforeningen.se Deutsche Alzheimer Gesellschaft – www.deutsche-alzheimer.de Stichting Alzheimer Nederland – www.alzheimer-nederland.nl Photos: Cathy Greenblat – www.cathygreenblat.com Design: Julian Howell Cover image This participant in the ARDSI day care centre in Cochin, India, was diagnosed with dementia at age 68 and was initially taken care of at home by family and domestic servants. Her aggressive behaviour became problematic, and she was enrolled in the daycare centre. At the centre she chats, tells stories and benefits from trained staff members and volunteers, such as Geetha, who are understanding and kind.
1 Alzheimer’s disease international World Alzheimer Report 2009
2 Preface Demographic ageing is a worldwide process that shows the successes of improved healthcare over the last century. Many are now living longer and healthier lives and so the world population has a greater proportion of older people. We all agree that ageing brings some challenges as well. Many international meetings have touched on this issue and adopted statements, for instance the Madrid International Plan of Action on Ageing from 2002. A clearly negative effect of ageing is the significant increase in the number of people with Alzheimer’s disease and related dementias. Alzheimer’s Disease International (ADI) has commissioned this report in order to support Alzheimer associations around the world in working with their governments on strategies to improve the lives of people with dementia and their carers, and to increase research efforts. To encourage the development of those national strategies, it is very important that the World Health Organization makes dementia a global health priority. If a country is in the business of supporting or spurring medical research, its portfolio ought to include funding Alzheimer’s disease research in a proportion that matches its burden to the country. To make clear why this is important and why it is urgent, we wanted to put together updated information on the prevalence and impact of the disease and offer a framework for solutions. Some recent experiences have been very encouraging. In 2004, Australia was the first country to make dementia a national health priority, and national dementia strategies have been launched in France, South Korea, England, Norway and the Netherlands. We also want to highlight a very recent initiative from the European Commission as the first international action plan on dementia. This report gives an overview and analysis of the situation, based on the currently available research data. The 2009 World Alzheimer Report confirms that there are many millions of people living with Alzheimer’s or another dementia. This report and all earlier studies indicate that the current number of people living with dementia is expected to grow at an alarming rate. ADI believes this report provides the best available estimates of dementia prevalence at a worldwide level. The scientists working on behalf of ADI used meta-analyses that produce estimates for all the world regions in the way that is explained in the full version of the report. ADI does not present estimates for individual countries and understands that different studies may be preferred to determine national prevalence figures. ADI encourages national Alzheimer prevalence research in individual countries; the use of those local results may be more accurate. It is clear that more research on the prevalence and impact of the disease is needed. ADI will therefore carry out follow up reports, beginning with economic data in 2010. We hope this will stimulate all those involved: governments, policy makers, healthcare professionals and Alzheimer associations, to work together on more and better solutions for dementia. With a new case of dementia in the world every seven seconds there is no time to lose. Daisy Acosta Marc Wortmann Chairman Executive Director Alzheimer’s Disease International Alzheimer’s Disease International
3
Contents
Key points 5
What is dementia? 13
Definitions, pathology and clinical features 14
Awareness 16
Aetiology (risk factors) 17
The course and outcome of dementia 18
The management of dementia 19
Structure of the report 20
References 21
Chapter 1 The global prevalence of dementia 25
Background 26
Methods 28
Results 30
Conclusions and recommendations 40
References 44
Chapter 2
The impact of dementia 47
The impact of dementia 48
Disability, dependency and mortality:
1 The Global Burden of Disease report 49
2 Other studies of disability and dependence 51
3 Adding years to life and life to years 53
The family and other informal carers 54
The cost of dementia 60
Summary and conclusion 63
References 65
Chapter 3 From recognition to action 67
From recognition to action 68
Global Alzheimer’s Disease Charter 68
Context 69
Dementia and services 71
Awareness raising and information 72
Capacity building 73
Quality 74
Risk reduction 74
Service development 75
Our vision for the future 76
Act now 77
References 78
Chapter 4 Recommendations 81
Appendices
Appendix 1 Global Burden of Disease (GBD) regions 84
Appendix 2 Alzheimer associations’ annual research expenditure budgets 86
Appendix 3 Comparison of the English and French dementia plans 87
Appendix 4 Comparison of dementia plans in Australia and South Korea 88
Glossary 89
Alzheimer’s Disease International 92
4
World Alzheimer ReporT 2009 · Alzheimer’s disease international 5
World Alzheimer Report
Key points
Jacqueline in a reminiscence
therapy session, 2008, Nice, France. Background: What is dementia? 6
Reminiscence therapy is based on
Chapter 1: The global prevalence of dementia 8
the evocation of older memories and
autobiographies. The sharing of these Chapter 2: The impact of dementia 9
memories, sometimes with the aid of
photographs and other objects, in a Chapter 3: From recognition to action 10
group helps to promote social exchanges, Chapter 4: Recommendations 11
and through this communication the
quality of life of people with dementia and
family carers is improved.6 Key points
Background
What is dementia?
1 Dementia is a syndrome due to disease of the brain, usually chronic,
characterised by a progressive, global deterioration in intellect including
memory, learning, orientation, language, comprehension and judgement.
2 While dementia mainly affects older people, there is growing awareness
of cases that start before the age of 65 years. After 65, the prevalence (the
proportion of people with the condition) doubles with every five-year increase in
age. Dementia is one of the major causes of disability in later life.
3 Dementia syndrome is linked to a large number of underlying brain pathologies.
Alzheimer’s disease, vascular dementia, dementia with Lewy bodies and
frontotemporal dementia are the most common.
4 The boundaries between these subtypes are indistinct, and mixed forms may be
the norm. The pathology (the changes that happen in the brain) with Alzheimer’s
disease develops over a long period of time, and the relationship between the
severity of the pathology and the presence (or absence) of dementia syndrome
is not clear. Other conditions that the person has, particularly cerebrovascular
disease (disease of the blood vessels supplying the brain) may be important.
5 Clinicians focus their diagnostic assessments on impairment in memory and
other cognitive functions, and loss of independent living skills. For carers, it
is the behavioural and psychological symptoms (BPSD) linked to dementia,
typically occurring later in the course of the disease, that are most relevant
and have most impact on their quality of life. Behavioural and psychological
symptoms are an important cause of strain on carers, and a common reason for
institutionalisation as the family’s coping reserves become exhausted.
6 Problem behaviours include agitation, aggression, calling out, sleep disturbance,
wandering and apathy. Around one quarter of people with dementia exhibit
apathy and a similar proportion show occasional signs of aggression.
Common psychological symptoms include anxiety, depression, delusions and
hallucinations. Around 25-40% have diagnosable affective disorder, and at least
10% have psychotic symptoms. The frequency and profile of these symptoms
seems to be similar between developed and developing country settings.
7 Awareness of dementia, as an organic brain condition, is inadequate worldwide.
The problem is stigmatised, so it is not discussed. If it is acknowledged then
it is often dismissed as a normal part of ageing, or viewed as a problem for
which nothing can be done. These three factors conspire to create a culture in
which help is neither sought nor offered. Alzheimer’s Disease International has
identified raising awareness of dementia among the general population and
health workers as a global priority.
8 The main risk factor for most forms of dementia is advanced age, with
prevalence roughly doubling every five years over the age of 65. Onset before
this age is relatively uncommon and, in the case of Alzheimer’s disease, often
suggests a genetic cause. Single gene mutations at one of three loci (beta
amyloid precursor protein, presenilin1 and presenilin2) account for many of
these cases.World Alzheimer ReporT 2009 · Alzheimer’s disease international 7
9 For late-onset Alzheimer’s disease both environmental (lifestyle) and genetic
factors are important. A common genetic polymorphism, the apolipoprotein E
(apoE) gene e4 allele, greatly increases risk of going on to develop dementia.
Epidemiological studies partly support associations between limited education,
head injury and depression, and both Alzheimer’s disease and dementia, but it
is not clear if these are causal.
10 The evidence for a causal role for cardiovascular risk factors and cardiovascular
disease in dementia and Alzheimer’s disease is very strong. Those with
high cardiovascular risk scores (incorporating hypertension, diabetes, high
cholesterol and smoking) have an increased risk for dementia incidence
whether exposure is measured in midlife or a few years before dementia onset.
Atherosclerosis (hardening of the arteries) and Alzheimer’s disease may be
linked disease processes with common underlying factors.
11 Unfortunately, attempts to modify cardiovascular risk exposure, by using
cholesterol lowering drugs (statins) and antihypertensives, have so far been
unsuccessful in reducing the incidence of dementia. This may well have been
a case of ‘too little, too late’. Hormone replacement therapy had an adverse
effect, and a trial of non-steroidal anti-inflammatory drugs (NSAIDs) had to be
stopped because of concerns regarding adverse effects.
12 Effective primary prevention of dementia is a realistic aspiration. However,
much more research is needed to understand better how and when lifestyle
factors influence the risk for developing dementia, informing more effective
prevention strategies.
13 The principal goals for dementia care are:
• early diagnosis
• optimising physical health, cognition, activity and well-being
• detecting and treating behavioural and psychological symptoms
• providing information and long-term support to carers
The person with dementia needs to be treated at all times with patience
and respect for their dignity and personhood. The carer needs support and
understanding – their needs should also be determined and attended to. Both
parties need to be supported to continue for as long as practicable with their
lives and in their own communities – living well with dementia.
14 Currently, there are no treatments available that cure, or even alter the
progressive course of dementia, although numerous new therapies are being
investigated in various stages of clinical trials. When effective new therapies
are developed, there will be enormous ethical and practical challenges with
respect to making such treatments widely and equitably available, particularly
to the two-thirds of people with dementia who live in low and middle income
countries.
15 Partially effective treatments are available for most core symptoms of dementia.
These treatments are symptomatic, that is they can improve a particular
symptom, but do not alter the progressive course of the disease. Importantly,
psychological and psychosocial therapies (sometimes referred to as ‘non-
pharmacological’ interventions) may be as effective as drugs in many areas, but
have been less extensively researched, and much less effectively promoted.
The research evidence on dementia care comes, overwhelmingly, from high
income countries.8 Key points
16 People with dementia and their carers can be educated about dementia,
countering lack of understanding and awareness about the nature of the
problems faced. They can also be trained to better manage most of the
common behavioural symptoms, in such a way that their frequency or the strain
experienced by the carer is reduced. Above all, the person with dementia and
the family carers need to be supported over the longer term.
Chapter 1
The global prevalence of dementia
1 We have conducted a new systematic review of the global prevalence of
dementia, identifying 147 studies in 21 Global Burden of Disease (GBD) world
regions.
2 We estimate 35.6 million people with dementia in 2010, the numbers nearly
doubling every 20 years, to 65.7 million in 2030 and 115.4 million in 2050.
3 Previous ADI estimates, published in The Lancet in 2005, were based on expert
consensus. A large number of new studies, particularly from low and middle
income countries, have enabled us now to conduct quantitative meta-analyses
in 11 of the 21 GBD world regions. Our new estimates are 10% higher. We
believe these to be more robust and valid figures.
4 When compared with our earlier Lancet/ADI consensus estimates those for
three regions were higher - Western Europe (7.29% vs. 5.92%), South Asia
(5.65% vs. 3.40%) and Latin America (8.50% vs. 7.25%). Those for East Asia
were lower (4.98% vs. 6.46%).
5 58% of all people with dementia worldwide live in low and middle income
countries, rising to 71% by 2050.
6 Proportionate increases over the next twenty years in the number of people
with dementia will be much steeper in low and middle income countries
compared with high income countries. We forecast a 40% increase in numbers
in Europe, 63% in North America, 77% in the southern Latin American cone
and 89% in the developed Asia Pacific countries. These figures are to be
compared with 117% growth in East Asia, 107% in South Asia, 134-146% in the
rest of Latin America, and 125% in North Africa and the Middle East.
7 A recent marked increase in the number of studies from low and middle income
countries has been accompanied by a sharp decline in prevalence research in
high income countries. In many high income countries, the evidence-base is
fast becoming out of date and more studies are needed.
8 The quality of many of the studies was relatively poor, although this is steadily
improving. A particular concern is the 49% of all studies that used, but
misapplied, a research design with two or more phases. This error is likely to
lead to an underestimate of true prevalence. However, for two phase studies in
general, a higher prevalence was observed, probably because of loss to follow-
up in the interval between the screening and definitive diagnostic assessments.
57% of all studies lacked a properly comprehensive dementia diagnostic work up.World Alzheimer ReporT 2009 · Alzheimer’s disease international 9
Chapter 2
The impact of dementia
1 According to the Global Burden of Disease report, dementia accounts for 4.1% of
total disease burden (Disability Adjusted Life Years) among people aged 60 years
and over, 11.3% of years lived with disability and 0.9% of years of life lost.
2 Among the other chronic non-communicable diseases, dementia accounts for
11.9% of years lived with disability (the second most burdensome chronic condition)
and 1.1% of years of life lost. The leading causes of death are heart disease (32.9%
of years of life lost) and cancer (22.5%). However, these are only 8th and 9th in the
rank of disabling conditions.
3 Research from North America, and recent findings from the 10/66 Dementia
Research Group’s population-based studies in Latin America, India and China
indicate, consistently, that dementia is the leading cause of dependency (needs for
care) and disability among older people.
4 Among the chronic diseases, prioritisation seems to be determined more by
contributions to mortality than to disability. Health spending and investment in
research is very much higher for cancer and heart disease than for dementia and
stroke. Chronic diseases that contribute most to mortality have the largest number
of research papers focussed on them, but the chronic diseases that contribute most
to disability are the subjects of the fewest research papers.
5 At some stage in the disease process, most if not all people with dementia require
some form of care. In all parts of the world this is generally provided by informal
(family) carers. According to the Alzheimer’s Association’s 2009 Alzheimer’s Disease
Facts and Figures, it is estimated that almost 10 million Americans provide unpaid
care for a person with Alzheimer’s disease or another dementia.
6 While there are many positive aspects of caring, carers of people with dementia are
very likely to experience strain. 40-75% have significant psychological illness, and
15-32% clinically diagnosable major depression. There may also be physical health
consequences - strained carers have impaired immunity and a higher mortality rate.
7 Among carers in general, caring for a person with dementia is particularly stressful.
Typically, they provide more intensive and extensive care, experience more strain,
and have higher levels of psychological illness.
8 Carers and those who live with people with dementia are twice as likely as others to
have significant psychological illness (controlling for the presence of other physical
and mental disorders).
9 In high income countries, the direct costs of dementia care exceed informal care
costs, with the cost of institutional care in care homes dominating in this category.
In the United Kingdom, for example, residential care homes contribute 41% of the
total costs, compared with 15% for care in the community, 8% for health care and
36% for informal care.10 Key points
10 Worldwide, the annual economic cost of dementia has been estimated as
US$315 billion. The total annual costs per person with dementia have been
estimated as US$1,521 in a low income country, rising to US$4,588 in middle
income countries, and US$17,964 in high income countries.
11 While only 38% of the people with dementia live in high income countries, 72%
of the costs arise from these regions. Informal (family) care is more important
in resource-poor countries, where there are few formal health or social care
services available. Informal care accounts for 56% of costs in low income
countries, 42% in middle income countries, and just 31% in high income
countries.
12 In the United Kingdom, the societal cost of dementia (£17.0 billion/US$27.2
billion) exceeds that for stroke, heart disease and cancer combined when
calculated on a like-for-like basis (£13.8 billion/US$22.0 billion), and is only a
little less when the lost productivity from premature mortality linked to cancer,
heart disease and stroke is included in the calculations (£19.9 billion/US$31.8
billion).
13 Demographic and social trends allow us to predict with reasonable certainty
that the ‘indirect’ costs of care, effectively a subsidy provided by families, will
increasingly be felt as ‘direct’ costs with real impacts on national budgets.
This will particularly be the case for low and middle income countries, where
dementia is not a priority and there are very few examples of national policies
and plans for the financing or provision of long-term care.
Chapter 3
From recognition to action
1 Dementia is a challenge for governments throughout the world; it is also an
opportunity to provide accessible, affordable and good quality services that
meet the expectations and needs of people with dementia and their families.
2 For low and medium income countries there is the opportunity not to repeat
the mistakes of high income countries that have become over dependent on
institutional care.
3 Across the world there are immense disparities in healthcare expenditure and
the distribution of doctors and nurses. This has an impact on the capacity of
healthcare systems to respond to the growing number of people with dementia.
4 A seven stage model for planning dementia services is proposed. It reflects the
progressive nature of dementia and includes:
• Pre-diagnosis awareness raising
• Diagnosis
• Post-diagnosis information and support
• Co-ordination and care management
• Community services to care for people with dementia in their own homes
• Continuing care
• End of life palliative careWorld Alzheimer ReporT 2009 · Alzheimer’s disease international 11
5 A graduated approach for low and medium income countries is proposed
which focuses attention first on:
• Awareness raising and understanding
• Capacity building
• Basic service development through enhancing primary care services
6 The visions for service development in all countries need to encompass public
understanding and attitudes to dementia, skills and knowledge of the health
and care workforce and their organisational infrastructure, and the equitable
distribution of services.
7 Governments are urged to act now.
Chapter 4
Recommendations
1 The World Health Organization (WHO) should declare dementia a world health
priority.
2 National governments should declare dementia a health priority and develop
national strategies to provide services and support for people with dementia
and their families.
3 Low and medium income countries should create dementia strategies based
first on enhancing primary healthcare and other community services.
4 High income countries should develop national dementia action plans with
designated resource allocations.
5 Develop services that reflect the progressive nature of dementia.
6 Distribute services with the core principle of maximising coverage and ensuring
equity of access, to benefit people with dementia regardless of age, gender,
wealth, disability, and rural or urban residence.
7 Create collaboration between governments, people with dementia, their carers
and their Alzheimer associations, and other relevant Non-Governmental
Organisations and professional healthcare bodies.
8 More research needs to be funded and conducted into the causes of
Alzheimer’s disease and other dementias, pharmacological and psychosocial
treatments, the prevalence and impact of dementia, and the prevention of
dementia.12
World Alzheimer ReporT 2009 · Alzheimer’s disease international 13
World Alzheimer Report
Introduction
What is dementia?
Daphne and her grandmother, Lara,
visited Lara’s mother, Margie, for the
Definitions, pathology and clinical features 14
Thanksgiving celebration at a Silverado
Senior Living Alzheimer’s community Awareness 16
in Houston, Texas. Daphne was
saddened by Margie’s loss of verbal Aetiology (risk factors) 17
communication skills. Lara convinced The course and outcome of dementia 18
Daphne to tell her about the piano
recital she would give the next day. The management of dementia 19
After the connection was made, Margie
signalled non-verbally that she had
Structure of the report 20
heard her great-granddaughter’s story. References 2114 What is dementia
Definitions, pathology and clinical features
The definition of dementia progressive course of the disorder is not possible.
Nevertheless, symptomatic treatments and support
Dementia is a syndrome due to disease of the brain,
can help people with dementia and carers alike.
usually chronic, characterised by a progressive, global
deterioration in intellect including memory, learning, The relative frequencies of the different subtypes
orientation, language, comprehension and judgement. of dementia are open to debate. Some of the rarer
It mainly affects older people, but, according to subtypes tend to be over-represented in case series
different estimates, between 2% and 10% of all from specialist clinical centres, as the unusual nature
cases start before the age of 65 years. After this the of the presentation predisposes both to help-seeking
prevalence doubles with every five year increment in and referral. A more fundamental problem is that the
age. Dementia is one of the major causes of disability borders between these different subtypes are by
in late-life. no means distinct. Clinico-pathological correlation
studies examine the agreement between the
The relationship between brain diagnosis made in life, and the pathology evident in
pathology and dementia syndrome the brain post-mortem. These have tended to indicate
that mixed pathologies are much more common than
Dementia syndrome is linked to a very large number
‘pure’ – this is particularly true for Alzheimer’s disease
of underlying brain pathologies. Alzheimer’s disease,
and vascular dementia, and Alzheimer’s disease
vascular dementia, dementia with Lewy bodies
and dementia with Lewy bodies (1). In one large case
and frontotemporal dementia are the commonest.
series of over 1000 post-mortems (2), while 86% of
The characteristic symptoms and neuropatholgical
all those with dementia had Alzheimer’s disease
findings are summarised in Table 1. Some rare
related pathology, only 43% had pure Alzheimer’s
underlying causes of dementia (subdural haematoma,
disease. 26% had mixed Alzheimer’s disease and
normal pressure hydrocephalus, hypercalcaemia,
cerebrovascular pathology and 10% had Alzheimer’s
and deficiencies of thyroid hormone, vitamin B12 and
disease with cortical Lewy bodies. Findings were
folic acid) are particularly important to detect since
similar among those who had been given a clinical
they may be treated effectively by timely medical
diagnosis of Alzheimer’s disease. ‘Pure’ vascular
or surgical intervention. Otherwise, altering the
dementia was comparatively rare (7.3%). Uncommon
Table 1
Characteristics of dementia subtypes
Dementia subtype Early, characteristic symptoms Neuropathology Proportion of
dementia cases
Alzheimer’s disease Impaired memory, apathy and depression Cortical amyloid plaques and 50-75%
(AD) * Gradual onset neurofibrillary tangles
Vascular dementia Similar to AD, but memory less affected, Cerebrovascular disease 20-30%
(VaD) * and mood fluctuations more prominent Single infarcts in critical regions,
Physical frailty or more diffuse multi-infarct
Stepwise onset disease
Dementia with Lewy Marked fluctuation in cognitive ability Cortical Lewy bodiesWorld Alzheimer ReporT 2009 · Alzheimer’s disease international 15
subtypes of dementia; frontotemporal dementia, disturbances in the past month. Apathy (27%),
Creutzfeld Jakob and Huntington’s disease tended depression (24%), and agitation/aggression (24%)
to have been misdiagnosed in life as Alzheimer’s were the most common symptoms, and these were
disease. Population-based studies have suggested around four times more common in those with
that frontotemporal dementia and vascular dementia dementia than in those without it (8). Participants with
are relatively common diagnoses in men with an Alzheimer’s disease were more likely to have delusions
early onset of dementia. Alzheimer’s disease tends and less likely to have depression. Agitation and
to predominate over vascular dementia among older aggression were more common in participants with
people with dementia, particularly among women (3). advanced dementia. In the 10/66 Dementia Research
Group pilot studies (6), behavioural and psychological
Another complicating factor is that many people
symptoms seemed to be just as common in low and
with Alzheimer’s disease pathology in the brain do
middle income countries. In a sample of 555 carers
not show signs of dementia. In part, this is because
from 21 centres in Latin America, India, China and SE
the brain changes underlying Alzheimer’s disease
Asia and Nigeria, 71% reported at least one problem
probably develop over a period of at least 20‑30 years
behaviour. The people with dementia were also
before symptoms become noticeable. Autopsies
assessed, and significant psychological symptoms
conducted on people who have died at various ages
were detected in half; 44% were diagnosed with
suggest that the earliest signs are noted around the
depression, 14% with anxiety disorder, and 11% with
base of the brain in the fifth decade of life, plaques
psychotic symptoms (delusions or hallucinations). In
and tangles later spreading up to the cortical
some respects the developing country carers were
regions (4). Dementia is conventionally diagnosed when
more disadvantaged. Given the generally low levels
cognitive decline affects a person’s ability to carry
of awareness about dementia as an organic brain
out important routine activities. Criteria for prodromal
disease (see below), they often could not understand
syndromes, for example ‘mild cognitive impairment
their relative’s condition, and tended to misinterpret
(MCI)’, have been proposed with a view to exploring
BPSD as deliberate misbehaviour on the part of the
interventions to delay or prevent dementia in those at
person with dementia (9). Others tended to blame the
high risk of progression. Also, findings from the Nun
carers for the distress and disturbed behaviour of the
Study in the USA suggest that vascular damage may
person for whom they were caring (10).
act as a cofactor, accelerating the onset of clinically
significant symptoms in people with underlying
Alzheimer’s disease pathology, which would otherwise
be asymptomatic (5).
Clinical features – the importance of
behavioural and psychological symptoms
of dementia
When making a diagnosis, clinicians focus their
assessments on impairment in memory and other
cognitive functions, and loss of independent
living skills. For carers, it is the behavioural and
psychological symptoms (BPSD) linked to dementia
that are most relevant and impact most on quality of
life. Problem behaviours include agitation, aggression,
calling out, sleep disturbance, wandering and
apathy. Common psychological symptoms include
anxiety, depression, delusions and hallucinations.
Most studies indicate that BPSD are an important
cause of carer strain (6), and a common reason for
institutionalisation as the family’s coping reserves
become exhausted (7). BPSD occur most commonly
in the middle stage of dementia (see also Course and
Outcome). In the population-based Cache County
study in the USA, 61% of people with dementia had
exhibited one or more behavioural or psychological16 What is dementia
Awareness
Dementia, and Alzheimer’s disease have been reliably High income countries
identified in all countries, cultures and races in which
The problem of low awareness is certainly not limited
systematic research has been carried out. However,
to low and middle income countries. For example,
levels of awareness vary enormously. Alzheimer’s
the National Dementia Strategy for the UK highlights
Disease International has identified raising awareness
stigma (preventing discussion of the problem) and two
of dementia among the general population and among
false beliefs (that dementia is a normal part of ageing,
health workers as a global priority (11).
and that nothing can be done) as the main factors
linked to inactivity in seeking or offering help (15). In the
Low and middle income countries
UK, people typically wait three years before reporting
Three studies from India (with a mixture of focus symptoms of dementia to their doctor, 70% of carers
group discussion and open-ended interviews) report being unaware of the symptoms of dementia
illustrate the pervasive problem in low and middle before diagnosis, and 58% of carers believe the
income countries (9;12;13). The typical features of symptoms to be just a normal part of ageing (16). Only
dementia are widely recognized, and indeed named 31% of primary care doctors believe that they have
‘Chinnan’ (literally childishness) in Kerala (9), ‘nerva received sufficient training to diagnose and manage
frakese’ (tired brain) in Goa (13), and ‘weak brain’ in dementia (17).
Banares (12). However, in none of these settings was
there any awareness of dementia as an organic brain Actions to improve awareness
syndrome, or indeed as any kind of medical condition.
In developed countries dementia awareness is
Rather, it was perceived as a normal, anticipated
growing rapidly, with the news media playing an
part of ageing. This general lack of awareness has
important part; coverage over 18 months in the UK
important consequences:
Daily Telegraph has increased from 57 articles in
1 Help from formal medical care services is not 1998/9 (18) to 112 when re-examined in 2006/7 (19).
sought (13). Recent evidence-based reports from the UK and
the Australian Alzheimer associations garnered
2 There is no structured training on the recognition
considerable media attention and were instrumental in
and management of dementia at any level of the
making dementia a national priority in both countries
health service.
(see Chapter 3). In France, the new president
3 There is no constituency to place pressure on the launched a national plan in 2008.
government or policy makers to start to provide
Public awareness in low and middle income countries
more responsive dementia care services (9).
is less developed, with few media outlets carrying
4 While families are the main caregivers, they must stories about dementia and ageing – a search in
do so with little support or understanding from 1999 of The Times of India identified no articles (18).
other individuals or agencies. 10/66 Dementia Research Group teams in Argentina,
Venezuela, Peru, Dominican Republic and India have
In the absence of understanding regarding its
succeeded in getting the message out in newspapers,
origins, dementia is stigmatized. In Goa, the likely
TV and radio (http://www.alz.co.uk/1066/1066_in_
causes were cited as ‘neglect by family members,
the_news.php). The Times of India published 15
abuse, tension and lack of love’ (13). In Kerala, it was
articles in the last 18 months alone. Our experience is
reported that most carers tended to misinterpret
that while media in low and middle income countries
symptoms of the disease and to designate these
are receptive to these stories as part of their role in
as deliberate misbehaviour by the person with
informing the public and stimulating debate, efforts
dementia (9). Sufferers are specifically excluded from
are required to alert them to the importance of ageing
residential care, and often denied admission to
and dementia, and to build their capacity to report
hospital facilities (13). Disturbed behaviour, common
research and understand its local relevance.
among people with dementia, is particularly poorly
understood leading to stigma, blame, and distress for
carers (14).World Alzheimer ReporT 2009 · Alzheimer’s disease international 17
Aetiology (risk factors)
Established risk factors Attempts at primary prevention
The main risk factor for most forms of dementia is A main aim of epidemiological research is to identify
advanced age, with prevalence roughly doubling every modifiable risk factors. Removing these risk factors through
five years over the age of 65. Onset before this age is very preventive interventions can then reduce the incidence of the
unusual and, in the case of Alzheimer’s disease, often disease. Epidemiological cohort studies indicated protective
suggests a genetic cause. Single gene mutations at one effects of non-steroidal anti-inflammatory drugs (NSAIDs),
of three loci (Beta amyloid precursor protein, presenilin1 hormone replacement therapy (HRT) and cholesterol
and presenilin2) account for most of these cases. For lowering therapies (statins). However, a randomised
late-onset Alzheimer’s disease both environmental controlled trial of HRT as a preventive therapy in post-
(lifestyle) and genetic factors are important. A common menopausal women indicated, against expectation, that it
genetic polymorphism, the apolipoprotein E (apoE) gene raised rather than lowered the incidence of dementia (41). The
e4 allele, greatly increases risk of going on to suffer two trials of statins have showed no preventive benefit (42).
from dementia; up to 25% of the population has one or The ADAPT trial of NSAIDs had to be stopped because of
two copies (20;21). However, it is not uncommon for one warnings of cardiovascular adverse effects in another trial
identical twin to suffer from dementia, and the other not. of NSAIDs (43). Antihypertensive treatment also seems to be
This implies a strong influence of the environment (22). ineffective as a preventive strategy (44).
Evidence from cross-sectional and case-control studies
suggest associations between Alzheimer’s disease More research needed
and limited education (23), and head injury (24;25), which,
The disappointing results from preventive intervention
however, are only partly supported by longitudinal (follow-
trials to date indicate that, despite much research, we still
up) studies (26). Depression is a risk factor in short term
understand far too little about the environmental and lifestyle
longitudinal studies, but this may be because depression
factors linked to dementia and Alzheimer’s disease. It may
is an early presenting symptom, rather than a cause of
be that our focus upon research in the developed West
dementia (27).
has limited possibilities to identify risk factors. Prevalence
and incidence of Alzheimer’s disease seems to be much
Modifiable risk factors – cardiovascular
lower in some developing regions. This may be because
risk factors and cardiovascular disease
some environmental risk factors are much less prevalent
Despite occasional negative findings from large in these settings – for example, African men tend to have
prospective studies (28;29), the accumulated evidence for good cardiovascular health with low cholesterol, low blood
a causal role for cardiovascular risk factors (CVRF) and pressure and low incidence of heart disease and stroke.
cardiovascular disease (CVD) in the aetiology of dementia Conversely some risk factors may only be apparent in low
and Alzheimer’s disease is very strong. In short (30-32) and middle income countries, as they are too infrequent in
and longer latency (33;34) incidence studies, smoking the developed economies for their effects to be detected.
increases the risk for Alzheimer’s disease. Diabetes is For example, in low and middle income countries dietary
also a risk factor (35), and in longer term cohort studies, deficiencies, particularly of micronutrients, are widespread
midlife hypertension (36;37) and hypercholesterolaemia (37) and strongly linked to poverty. Deficiencies of folate
are associated with Alzheimer’s disease onset in later life. and vitamin B12 are of particular interest given their
Those with high cardiovascular risk scores (incorporating consequences: anaemia, raised homocysteine levels (45),
hypertension, diabetes, hypercholesterolaemia and increased risk of stroke and ischaemic heart disease (46).
smoking) have an increased risk for dementia incidence Vitamin B12 deficiency is very common (> 40%) across Latin
whether exposure is measured in midlife (34) or a few America (47-49). Folate deficiency is endemic in those living
years before dementia onset (32). Recent studies report in poverty (48), and after economic crisis (49). Micronutrient
associations between metabolic syndrome and incident deficiency is probably even more common in older people
cognitive decline (38), and insulin resistance and impaired but there are few data on this age group (47). Research on
executive function (39). These findings have led to the micronutrients and dementia in developed countries has
hypothesis that atherosclerosis and Alzheimer’s disease focussed upon antioxidants (50) with less attention towards
are linked disease processes (40), with several common deficiencies in vitamin B12 and folate (51-54). Available studies
underlying factors (the apoE e4 gene, hypertension, were small in size and provide inconsistent findings – two
increased fat intake and obesity, raised cholesterol, out of three studies testing for an effect of folate deficiency
diabetes, the metabolic syndrome, smoking and systemic on dementia risk were positive (51;52), B12 was associated
inflammation). in only one out of four studies (52). Anaemia, strongly linked
to undernutrition, has been identified as a risk factor for
dementia in India (6), and needs to be explored elsewhere.18 What is dementia
The course and outcome of dementia
Dementia affects every person in a different way. Middle stage
Its impact can depend on what the person was like
As the disease progresses, limitations become clearer
before the disease; their personality, their lifestyle,
and more restricting. The person with dementia has
their significant relationships and their physical health.
difficulty with day-to-day living and:
The problems linked to dementia can be best
• May become very forgetful – especially of recent
understood in three stages:
events and people’s names
1 Early stage – first year or two
• Can no longer manage to live alone without
2 Middle stage – second to fourth or fifth years problems
3 Late stage – fifth year and after • Is unable to cook, clean or shop
These times are given as guidelines only – sometimes • May become extremely dependent on their family
people can deteriorate more quickly, sometimes more and caregivers
slowly.
• Needs help with personal hygiene, i.e. toilet,
Dementia reduces the lifespan of affected people. washing and dressing
In the developed West a person with dementia can
• Has increased difficulty with speech
expect to live for roughly 5-7 years after onset/
diagnosis (56;57). In low and middle income countries, • Shows problems with wandering and other
diagnosis is often much delayed, and survival may behaviour problems such as repeated questioning
be much shorter (58). Again, of course, there is much and calling out, clinging and disturbed sleeping
individual variation – some may live for longer,
• Becomes lost at home as well as outside
and some may live for shorter times because of
intercurrent health conditions. • May have hallucinations (seeing or hearing things
which aren’t really there)
Not all people with dementia will display all the
symptoms described below. Nevertheless, a summary
Late stage
of this kind can help carers to be aware of potential
problems and to allow them to think about future care This stage is one of near total dependence and
needs. inactivity. Memory disturbances are very serious
and the physical side of the disease becomes more
Early stage obvious. The person may:
The early stage of dementia is often overlooked. • Have difficulty eating
Relatives and friends (and sometimes professionals
• Be incapable of communicating
as well) see it as ‘old age’; just a normal part of the
ageing process. Because the onset of dementia is • Not recognise relatives, friends and familiar objects
gradual, it is often difficult to be sure exactly when it
• Have difficulty understanding what is going on
begins. The person may:
around them
• Have problems talking properly (language
• Be unable to find their way around in the home
problems)
• Have difficulty walking
• Have significant memory loss – particularly for
things that have just happened • Have bladder and bowel incontinence
• Not know the time of day or the day of the week • Display inappropriate behaviour in public
• Become lost in familiar places • Be confined to a wheel chair or bed
• Have difficulty in making decisions
• Become inactive and unmotivated
• Show mood changes, depression or anxiety
• React unusually angrily or aggressively on
occasion
• Show a loss of interest in hobbies and activitiesWorld Alzheimer ReporT 2009 · Alzheimer’s disease international 19
The management of dementia
Guiding principles effective as drugs in many areas, but have been less
extensively researched, and much less effectively
The principal goals of dementia management and
promoted. The evidence base for dementia care
care:
comes, overwhelmingly, from high income countries.
• Early diagnosis
Treatments for Cognitive impairment
• Optimising physical health, cognition, activity and
Cholinesterase Inhibitors (ChEIs) (60-62) and
well-being
NDMA receptor antagonists (63) can lead to
• Detecting and treating behavioural and useful improvements in cognitive function. Cost-
psychological symptoms effectiveness is by no means established (64), and
recommendations regarding their use will depend
• Providing information and long-term support to
upon affordability and availability of specialist
carers
support. Costs of ChEls are reimbursed in some
The person with dementia needs to be treated at all countries and regions but not all. Cheaper ‘generic’
times with patience and respect for their dignity and ChEIs are available in India. Patent law is side-
personhood. The carer needs unconditional support stepped by Huperzine A, a cheap plant extract with
and understanding – their needs should also be similar properties used in China (58). The evidence-
determined and attended to. Carers can be educated base from low and middle income countries is limited
about dementia, countering lack of understanding and to one small RCT of donepezil in Brazil (65) and open-
awareness about the nature of the problems faced. label trials of galantamine in Brazil (66) and China (67).
They can also be trained to better manage most of the More development and research is needed to see if
common behavioural symptoms, in such a way that reminiscence therapy (68), cognitive stimulation (69;70)
their frequency and/or the strain experienced by the and rehabilitation (71) could be feasible and effective
carer is reduced. Above all, the person with dementia community interventions.
and the family carers need to be supported over the
longer term. Treatments for Behavioural and
psychological symptoms of dementia (BPSD)
The hope for a cure For BPSD, antipsychotic drugs are minimally
efficacious overall, although they may be very helpful
Currently, there are no treatments available that
for some patients (72-75), particularly those for whom
cure or even alter the progressive course of
aggression is a problem. There are serious concerns
dementia, although numerous new therapies are
about their safety with an increased risk of death (76)
being investigated in various stages of clinical
and cerebrovascular adverse events (74). Too little
trials. This is a very active and promising field for
research has been carried out to be clear about
drug development (59). Given that any new disease-
the potential benefits of SSRI antidepressants (77-79)
modifying agent would be likely to be very expensive,
and carbamezepine (80;81). For these reasons, drug
thought should be given now to the huge ethical
treatment cannot be recommended as first-line
and practical challenges involved in making such a
management, other than with specialist input, for
treatment widely and equitably available, particularly
severe and distressing behaviour disturbance where
to the two-thirds of people with dementia living in low
there is clear and imminent risk of harm. Physical
and middle income countries. This problem is being
health assessment, carer training and support are all
addressed with respect to antiretroviral drugs for
indicated. More research is needed into the potential
HIV/AIDS through an unprecedented global alliance,
benefits of simple low-cost strategies, easily applied
led by the Global Fund and US Presidential PEPFAR
by carers at home; for example massage (82;83) and
initiatives.
aroma therapy (84).
Current evidence-based treatments
The importance of carer interventions
Partially effective treatments are available for most
A large literature attests to the wide-ranging potential
core symptoms of dementia. These treatments
benefits of carer interventions in dementia (85). Carer
are all symptomatic, that is they can ameliorate a
interventions include:
particular symptom, but do not alter the progressive
course of the disease. Importantly, psychological and • Psychoeducational interventions, many of which
psychosocial interventions (sometimes referred to include an element of carer training
as ‘non-pharmacological’ interventions) may be as20 What is dementia
Structure of the report
• Psychological therapies, e.g. cognitive behavioural Chapter 1: The global prevalence of dementia
therapy (CBT), and counselling describes the systematic review of the world literature
on the prevalence of dementia, the approach used
• Carer support
to generate new prevalence estimates for the 21
• Respite care Global Burden of Disease regions, and the estimated
numbers of people with dementia in each region with
Many interventions combine several of these
projections from 2010 to 2050.
elements. There are several systematic reviews and
meta-analyses (86-90). Outcomes studied include Chapter 2: The impact of dementia
carer strain, depression and subjective well-being; provides information regarding the impact of
behaviour disturbance and mood in the care recipient; dementia, at the level of the individual, the family and
and institutionalisation. wider society; the evidence on the contribution of
dementia, compared with other chronic diseases, to
Most carer interventions seemed to benefit carer
disability, mortality and dependence is summarised;
strain and depression, CBT having the largest impact
the care arrangements for people with dementia
on depression. Psychoeducational interventions
in many world regions, and the strain experienced
required the active participation of the carer (for
by their carers are described; finally the impact of
example in role-playing activities) to be effective (86).
dementia and other chronic diseases in terms of the
Carer support interventions seemed only to be
societal economic cost is summarised.
efficacious in increasing carer well-being (86). For
respite care, non-randomised interventions suggest Chapter 3: From recognition to action
significant reductions in carer strain and psychological sets out the challenges to be faced by governments
morbidity (86). While nearly all of the carer intervention and health systems worldwide to meet the needs of
trials to date were conducted in high income the growing numbers of people living with dementia,
countries, two low and middle income trials of a their families and carers.
brief carer education and training intervention – the
Chapter 4: Recommendations
ADI/1066 ‘Helping Carers to Care’ intervention – were
offers recommendations built on the evidence base
published recently, one from India (91) and one from
set out in earlier chapters.
Russia (92). Although small in size, both indicated much
larger treatment effects than are typically seen in trials
of such interventions in high income countries, on
carer psychological morbidity (91) and strain (92).
Finally, there is clear evidence from the pooled
results of ten randomised controlled trials (90) that
carer interventions delay institutionalisation in high
income countries. People with dementia whose carer
received the intervention were 40% less likely to be
institutionalised over the follow-up period (OR=0.60,
95% CI=0.43-0.85). The effective interventions were
structured, intensive and multicomponent, offering
a choice of services and supports to carers (86;90).
Prevention or delay of institutionalisation confers a
substantial societal benefit given the very high costs
in high income countries (see Chapter 2).World Alzheimer ReporT 2009 · Alzheimer’s disease international 21
References for ‘What is dementia?’
1 Neuropathology Group. Medical Research Council 18 The 10/66 Dementia Research Group. Dementia in
Cognitive Function and Aging Study. Pathological correlates Developing Countries. A preliminary consensus statement
of late-onset dementia in a multicentre, community-based from the 10/66 Dementia Research Group. International
population in England and Wales. Neuropathology Group Journal of Geriatric Psychiatry 2000;15:14-20.
of the Medical Research Council Cognitive Function and
Ageing Study (MRC CFAS).[comment]. Lancet 2001 January 19 Prince M, Acosta D, Albanese E, Arizaga R, Ferri CP, Guerra
20;357(9251):169-75. M et al. Ageing and dementia in low and middle income
countries-Using research to engage with public and policy
2 Jellinger KA. Clinicopathological analysis of dementia makers. Int Rev Psychiatry 2008 August;20(4):332-43.
disorders in the elderly – an update. J Alzheimers Dis
2006;9(3 Suppl):61-70. 20 Saunders AM, Strittmatter WJ, Schmechel D, St.George-
Hyslop PH, Pericak-Vance MA, Joo SH et al. Association
3 Knapp, M and Prince M. Dementia UK – A report into the of apolipoprotein E allele e4 with late-onset familial and
prevalence and cost of dementia prepared by the Personal sporadic Alzheimer’s disease. Neurology 1993;43:1467-72.
Social Services Research Unit (PSSRU) at the London
School of Economics and the Institute of Psychiatry at 21 Nalbantoglu J, Gilfix BM, Bertrand P, Robitaille Y, Gauthier
King’s College London, for the Alzheimer’s Society. THE S, Rosenblatt DS et al. Predictive value of apolipoprotein
FULL REPORT. London: The Alzheimer’s Society; 2007. E genotyping in Alzheimer’s disease: results of an autopsy
series and an analysis of several combined studies. Ann
4 Braak H, Braak E. Evolution of neuronal changes in the Neurol 1994;36(6):889-95.
course of Alzheimer’s disease. [Review] [55 refs]. Journal of
Neural Transmission 1998;Supplementum. 53:127-40. 22 Breitner JC, Welsh KA, Gau BA, McDonald WM, Steffens
DC, Saunders AM et al. Alzheimer’s disease in the National
5 Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner Academy of Sciences-National Research Council Registry
PA, Markesbery et al. Brain infarction and the clinical of Aging Twin Veterans. III. Detection of cases, longitudinal
expression of Alzheimer disease. The Nun Study [see results, and observations on twin concordance. Arch Neurol
comments]. JAMA 1997;277(10):813-7. 1995;52(8):763-71.
6 Ferri CP, Ames D, Prince M. Behavioral and psychological 23 Ott A, Breteler MM, van Harskamp F, Claus JJ, van der
symptoms of dementia in developing countries. Int Cammen TJ, Grobbee DE et al. Prevalence of Alzheimer’s
Psychogeriatr 2004 December;16(4):441-59. disease and vascular dementia: association with
education. The Rotterdam study [see comments]. BMJ
7 de Vugt ME, Stevens F, Aalten P, Lousberg R, Jaspers N,
1995;310(6985):970-3.
Verhey FR. A prospective study of the effects of behavioral
symptoms on the institutionalization of patients with 24 Mortimer JA, van Duijn CM, Chandra V, Fratiglioni L, Graves
dementia. Int Psychogeriatr 2005 December;17(4):577-89. AB, Heyman A et al. Head trauma as a risk factor for
Alzheimer’s disease: a collaborative re-analysis of case-
8 Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens
control studies. EURODEM Risk Factors Research Group.
DC, Breitner JC. Mental and behavioral disturbances
Int J Epidemiol 1991;20 Suppl 2:S28-35.
in dementia: findings from the Cache County Study on
Memory in Aging. Am J Psychiatry 2000 May;157(5):708-14. 25 Mayeux R, Ottman R, Maestre G, Ngai C, Tang MX,
Ginsberg H et al. Synergistic effects of traumatic head injury
9 Shaji KS, Smitha K, Praveen Lal K, Prince M. Caregivers
and apolipoprotein-epsilon 4 in patients with Alzheimer’s
Of Patients With Alzheimer’s Disease : A Qualitative Study
disease. [see comments.]. Neurology 1995 March;45(3 Pt
From The Indian 10/66 Dementia Research Network.
1):555-7.
International Journal of Geriatric Psychiatry 2002;18:1-6.
26 Stern Y, Gurland B, Tatemichi TK, Tang MX, Wilder D,
10 Ferri CP, Ames D, Prince M. Behavioral and psychological
Mayeux R. Influence of education and occupation on the
symptoms of dementia in developing countries. Int
incidence of Alzheimer’s disease [see comments]. JAMA
Psychogeriatr 2004 December;16(4):441-59.
1994;271(13):1004-10.
11 Graham N, Brodaty H. Alzheimer’s Disease International.
27 Devanand DP, Sano M, Tang MX, Taylor S, Gurland BJ,
International Journal of Geriatric Psychiatry 1997;12(7):691-
Wilder D et al. Depressed mood and the incidence of
2.
Alzheimer’s disease in the elderly living in the community.
12 Cohen L. Toward an anthropology of senility: anger, Arch Gen Psychiatry 1996;53(2):175-82.
weakness, and Alzheimer’s in Banaras, India. Med
28 Yip AG, Brayne C, Matthews FE. Risk factors for incident
Anthropol Q 1995;9(3):314-34.
dementia in England and Wales: The Medical Research
13 Patel V, Prince M. Ageing and mental health in a developing Council Cognitive Function and Ageing Study. A population-
country: who cares? Qualitative studies from Goa, India. based nested case-control study. Age Ageing 2006 January
Psychological Medicine 2001;31(1):29-38. 13.
14 Ferri CP, Ames D, Prince M. Behavioral and psychological 29 Bursi F, Rocca WA, Killian JM, Weston SA, Knopman
symptoms of dementia in developing countries. Int DS, Jacobsen SJ et al. Heart Disease and Dementia: A
Psychogeriatr 2004 December;16(4):441-59. Population-based Study. Am J Epidemiol 2006 January
15;163(2):135-41.
15 Department of Health. Living well with dementia. A National
Dementia Strategy. London, UK: Department of Health; 30 Ott A, Slooter AJC, Hofman A, van Harskamp F, Witteman
2009. JCM, Van Broeckhoven C et al. Smoking and risk of
dementia and Alzheimer’s disease in a population-based
16 Eisai Inc / Pfizer. Facing Dementia Survey. London: Eisai Inc cohort study: the Rotterdam Study. Lancet 1998;351:1841-3.
and Pfizer; 2004.
31 Juan D, Zhou DH, Li J, Wang JY, Gao C, Chen M. A 2-year
17 National Audit Office. Improving services and support for follow-up study of cigarette smoking and risk of dementia.
people with dementia. London: TSO; 2007. Eur J Neurol 2004 April;11(4):277-82.You can also read
